Featured Research

from universities, journals, and other organizations

Enzyme Found In Blood Vessels Likely Target To Treat Lung Injury

Date:

April 30, 2003

Source:

Northwestern University

Summary:

Scientists at Northwestern University have demonstrated that an enzyme vital to normal function of blood vessels also can be an Achilles heel during infection-induced or ventilator-induced lung injury. They believe that the enzyme holds significant potential as a drug discovery target for the treatment of acute lung injury.

Share This

Lung injury due to infection, such as in sepsis, accounts for hundreds of thousands of hospitalizations a year. Sepsis occurs in 2 percent of hospital admissions and is associated with a death rate of about 50 percent. Many of these patients require ventilation to support their breathing, which may in itself produce additional injury to the lung. Yet, there are few available treatments for lung injury associated with sepsis or ventilation.

Related Articles

Now, scientists at Northwestern University have demonstrated that an enzyme vital to normal function of blood vessels also can be an Achilles heel during infection-induced or ventilator-induced lung injury. They believe that the enzyme holds significant potential as a drug discovery target for the treatment of acute lung injury.

As described in the May issue of Proceedings of the National Academy of Sciences, Mark Wainwright, M.D., and D. Martin Watterson identified a molecule, called myosin light chain kinase 210 (MLCK 210), that makes endothelial cells in the lung susceptible to injury during periods of inflammation.

Wainwright is assistant professor of pediatrics at the Feinberg School of Medicine at Northwestern University and a researcher at the Children's Memorial Institute for Education and Research. Watterson is J.G. Searle Professor of Molecular Biology and Biochemistry, professor of molecular pharmacology and biological chemistry at the Feinberg School and director of the Northwestern University Drug Discovery Training Program.

Endothelial cells line blood vessels throughout the body and serve as a barrier to keep toxins in the blood from entering tissues and organs. MLCK 210 regulates normal endothelial cell function, but the contribution of MLCK 210 to the mechanisms of lung injury in the living animal was unknown.

Wainwright said that cell culture (or, in vitro) studies have identified several enzymes, including MLCK 210, in the regulation of endothelial barrier function, but no one had integrated the in vitro studies with disease injury and MLCK 210 function in a living animal.

Watterson genetically engineered mice that are missing the gene that codes for MLCK 210. The researchers exposed mice lacking MLCK 210 to a bacterial toxin that causes tissue injury as a result of severe infection. The MLCK 210 knockout mice are less susceptible to acute lung injury and also showed significant improvement in survival when exposed to a combination of toxin exposure and subsequent ventilator-induced injury.

This sequential injury is reminiscent of the clinical situation with life support for a critically ill patient.

The researchers also developed an MLCK inhibitor, an experimental drug that blocks the function of the enzyme, which they injected into normal mice with an intact MLCK 210 gene.

Normal mice exposed to bacterial toxin and ventilator-induced injury were protected by a single injection of the MLCK 210 inhibitor, a finding identical to that in the genetically altered mice lacking the MLCK 210 gene.

The researchers believe that their results and will enable scientists to conduct further studies involving the role of endothelial cells in heart disease, stroke and neurodegeneration, areas that the National Institutes of health has identified as a key research priority.

More From ScienceDaily

More Health & Medicine News

Featured Research

Mar. 3, 2015 — Adults over the age of 30 only catch flu about twice a decade, a new study suggests. So, while it may feel like more, flu-like illness can be caused by many pathogens, making it difficult to assess ... full story

Mar. 3, 2015 — No significant change in home habits of smokers have been observed in the aftermath of a ban on smoking in public spaces, researchers report. Greater inspiration to kick the habit likely comes from ... full story

Mar. 3, 2015 — Heart function has been associated with the development of dementia and Alzheimer's disease through a new study. Participants with decreased heart function, measured by cardiac index, were two to ... full story

Mar. 3, 2015 — Children of recently separated or divorced families are likelier to drink sugar-sweetened beverages than children in families where the parents are married, putting them at higher risk for obesity ... full story

Mar. 3, 2015 — Gastric bypass and similar stomach-shrinking surgeries are a popular option for obese patients looking to lose weight or treat type 2 diabetes. While the surgeries have been linked to a decreased ... full story

Mar. 3, 2015 — Most people consume more salt than they need and therefore have a higher risk of heart disease and stroke, which are the two leading causes of death worldwide. But a new study reveals that dietary ... full story

Mar. 3, 2015 — Twice as many children born to mothers who took antibiotics during pregnancy were diagnosed with asthma by age 3 than children born to mothers who didn’t take prenatal antibiotics, a new study has ... full story

Mar. 3, 2015 — Although sedatives are often administered before surgery, a randomized trial finds that among patients undergoing elective surgery under general anesthesia, receiving the sedative lorazepam before ... full story

Mar. 3, 2015 — Pediatric otolaryngologists and surgeons are concerned with parents getting the wrong message regarding the safety/desirability of letting babies and young children eat peanuts to prevent them from ... full story

Featured Videos

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) — After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3)
Video provided by AP

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) — Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13
Video provided by AFP

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) — A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3)
Video provided by AP

Related Stories

May 12, 2011 — New research investigates the therapeutic use of human stem cells from bone marrow against acute lung injury and identifies TNF-alpha-induced protein 6 as a major molecular component of stem cell ... full story

Jan. 4, 2011 — All of us may be able to breathe a little easier now that scientists have found a new therapeutic target for controlling dangerous inflammation in the lungs. New research suggests that blocking the ... full story

Oct. 13, 2010 — Researchers are investigating a potential new treatment for lung disease that could save many lives each year. They are studying how statins, drugs which are commonly used to treat high cholesterol, ... full story

ScienceDaily features breaking news and videos about the latest discoveries in health, technology, the environment, and more -- from major news services and leading universities, scientific journals, and research organizations.